Table 3.

Review of reported effects on inflammatory cascade in varying skin models upon exposure to PM

Model	PM type	Dose and application	Exposure time	Main findings	Ref.
Ex vivo human skin	SRM® 1649b	2 mg/cm2, topical	24 h	- Increased MMP-1 protein expression.	[119]
Mice, BALB/c	SRM® 1649b	100 μg/m2, topical	24 h repetitive exposure, 5 d total	- Increased COX2 protein expression.	[122]
	SRM® 1649b	100 μg/cm2, topical	24 h repetitive exposure, 5 d total	- Increased epidermal thickness. - Neutrophil infiltration. - Increased COX2 protein expression.	[179]
Mice, BALB/c with disrupted barrier	PM ≤1 μm from Seoul, Korea	8 μg/cm2, topical	6 h and 2 w repetitive exposures, 10 times in total	- Increased epidermal thickness in both skin types. - Neutrophil infiltration. - Increased mRNA expression of IL-8 functional homologs (KC, MIP2, LIX). - Increased mRNA expression MMP13.	[121]
Mice, NC/Nga, AE model	The soluble phase of DEP.	1 mg/time, topical	Repetitive exposure, every 1, 3, or 9 weeks in total	- Increased AE lesion formation. - Increased total IgE levels.	[226]
Mice, HR-1	SRM® 1650b	100 μg/mL, topical	7 d	- Increased epidermal thickness.	[124]
	SRM® 1650b	100 μg/mL, topical	7 d	- Increased epidermal thickness.	[168]
	SRM® 1650b	100 μg/mL, topical	7 d	- Increased IL-1β and IL-6 protein expression. - Increased TLR5 protein expression. - Increased MyD88 protein expression. - Increased phosphorylation of p65.	[169]
HSE	SRM® 2975	200 μg/mL, systemic	Every 2 d, 6 d total	- Decreased IL-8, CXCL10, and ICAM1 protein secretion.	[125]
HEE	CAPs, PM2.5	0.5 and 2.0 μg/cm2, topical	24 and 48 h	- Nuclear translocation of p65. - Increased IL-1α protein secretion. - Increased COX2 protein expression.	[128]
	CRM no. 28	25 mg, topical	6 and 24 h	- Upregulated mRNA expression of IL1A, IL1B, IL6, CXCL8, CCL20, MMP1, MMP3, MMP9, MMP12, and ICAM1 after 6 h. - Downregulated expression of tissue inhibitors of MMPs (2–4) after 6 h. - Induced IL-8 and MMP-1 protein secretion after 24 h.	[129]
	PM0.3–2.5 from Benin, West-Africa	15 and 30 μg/cm2, topical	24 h	- Increased IL-1α and IL-8 protein secretion. - Increased MMP-1 and MMP-3 protein expression.	[133]
	PM2.5 from Seoul, Korea	50 μg/mL, topical	24 h	- Increased MMP-1 protein expression.	[132]
	SRM® 1648a	2.2, 8.9, and 17.9 μg/cm2, topical	24 and 48 h	- Increased IL-1α protein secretion.	[131]
NHDF	SRM® 1649b	100–400 μg/mL, systemic	24 h	- Phosphorylation of ERK and JNK. - Increased MMP1 mRNA and protein expression.	[172]
	Diesel PM	30 and 60 μg/mL, systemic	24 h	- Increased MMP3 and MMP9 mRNA expression.	[138]
	SRM® 1649b	50 μg/mL, systemic	24 h	- Increased MMP1 mRNA expression.	[119]
	SRM® 2787	30 μg/cm2, systemic	24 h	- Increased IL-6 and IL-8 protein secretion. - Increased MMP-1 and decreased procollagen and TGF-β protein secretion. - Increased IL1B, IL6, CXCL8, and IL33 mRNA expression. - Increased MMP1 and MMP3 and decreased TGFB, collagen type I alpha 1 chain, collagen type I alpha 2 chain, and elastin mRNA expression.	[135]
	ERM-CZ100	200 μg/mL, systemic	24 h	- Increased MMP-1, −2,-8, −9, −13 protein expression. - Nuclear translocation of p65. - Phosphorylation of ERK, JNK, and p38.	[136]
	The pre-conditioned medium of HaCaT treated with CRM no. 28	125 μg/mL, systemic	30 m, 48 h post-incubation	- Increased PGE2, TNF-α, IL-1β, and IL-6 protein secretion. - Increased COX2 protein expression. - Nuclear translocation of p65. - Phosphorylation of p38, ERK, and JNK. - Increased MMP-1 and MMP-2 protein expression.	[137]
	Diesel PM	30 and 60 μg/mL, systemic	6 h	- Increased MMP2 and MMP9 mRNA expression.	[227]
NHDF and HaCaT co-culture	SRM® 1648a and SRM® 1649b	50 μg/cm2, systemic	24 h	- Phosphorylation of p38. - Increased IL1A, IL1B, IL6, and CXCL8 mRNA expression and protein secretion (HaCaT). - No changes in TNF mRNA expression and protein secretion (HaCaT). - Increased MMP1 and COX2 mRNA expression (NHDF).	[178]
NHEK	PM2.5 from Xi’an, China	50 μg/mL, systemic	24 h	- Top upregulated genes from transcriptomics analysis are CXCL1, IL1A, and IL1B.	[134]
	Diesel PM	30 and 60 μg/mL, systemic	24 h	- Increased IL1A, IL6, CXCL8, and TNF mRNA expression and protein secretion.	[138]
	ERM-CZ120	3, 10, 30 and 100 μg/mL, systemic	24 and 48 h	- Increased IL1B, IL6, CXCL8, and TNF mRNA expression after 24 h. - Increased IL-1β, IL-6, IL-8, and TNF-α protein secretion after 48 h. - Increased MMP1 mRNA expression and protein secretion after 24 h.	[173]
	SRM® 1650b	Unknown	24 h	- Increased IL-1β and IL6 protein secretion. - Increased IL-6 protein expression.	[169]
	PM ≤1 μm from Seoul, Korea	40 μg/cm2, systemic	24 h	- Increased CXCL8 mRNA expression and protein secretion. - Increased MMP1 mRNA expression and protein secretion.	[121]
	SRM® 2786	1 mg/mL, systemic	6 h	- RNA-Seq analysis: Upregulation of IL1B, IL36G, CXCL3, CXCL8, and IL1R2. Downregulation of MMP3 and MMP28.	[141]
	SRM® 1649b	50 μg/cm2, systemic	24 h	- Increased COX2 protein expression.	[181]
	SRM® 1649b	100 μg/mL, systemic	24 and 48 h	- Increased IL-8 protein secretion.	[228]
	Diesel PM	20 μg/mL, systemic	48 h	- Increased IL-1β and IL-8 protein secretion.	[229]
	Diesel PM	30 and 60 μg/mL, systemic	6 h	- Increased IL1A, IL6, CXCL8, and TNF mRNA expression.	[227]
	Asian dust storm particles from Seoul, Korea	25 μg/mL, systemic	24 h	- Increased IL6, CXCL8, and CSF2 mRNA expression. - No changes in IL1B, IFNG, and IL18 mRNA expression.	[139]
	PM2.5 from Seoul, Korea	25 μg/mL, systemic	24 h	- Top upregulated genes from transcriptomics analysis are IL1B, IL36G, IL1A, IL1R2, PTGS2, IRAK2, MMP1, MMP9, and MMP10. - Downregulated gene is CXCL14. - Induced IL-1α protein secretion. - Phosphorylation of p65 and p38.	[132]
HaCaT	CRM no. 28	125 μg/mL, systemic	30 m, 48 h post-incubation	- Increased PGE2, TNF-α, IL-1β, and IL6 protein secretion. - Increased COX2 protein expression. - Nuclear translocation of p65. - Phosphorylation of p38, ERK, and JNK. - Increased MMP-1 and MMP-2 protein expression.	[137]
	PM2.5 from Shanghai, China	10–100 μg/mL, systemic	24 h	- No changes in CSF2 protein secretion. - Increased TSLP, TNF-α, IL-1α, and IL-8 protein secretion.	[144]
	SRM® 1648a	50–200 ppm, systemic	24 and 48 h	- Increased TRPV1 mRNA and protein expression (via p38/MAPK and NF-κB pathway). - Increased IL-1β, IL-8, and TNF-α protein secretion.	[130]
	SRM® 1648a and SRM® 1649b	50 μg/cm2, systemic	24 h	- Induced phosphorylation of p-38.	[178]
	SRM® 1649b	50 μg/cm2, systemic	6 and 24 h	- Increased phosphorylation of ERK, p38, JNK, and Akt after 6 h. - Increased COX2, ICAM1, cPLA2, and PGE2 protein expression after 24 h. - Increased MMP-9 protein expression after 24 h.	[143]
	SRM® 1649b	50 μg/cm2, systemic	2 and 6 h	- Increased COX2 and MMP-9 protein expression. - Phosphorylation of ERK, JNK, and p38.	[142]
	SRM® 1649b	25 and 50 μg/cm2, systemic	4 and 24 h	- Increased COX2 protein expression. - Increased PGE2 and IL-6 protein secretion. - No changes in IL-24, IL-1β, and TNF-α protein secretion.	[122]
	SRM® 1649b	25–100 μg/cm2, systemic	4 and 24 h	- Increased COX2 protein (24 h) and mRNA (6 h) expression. - Increased PGE2 protein secretion after 24 h. - Nuclear translocation p65 after 4 h. - Phosphorylation of ERK, JNK, and p38 after 4 h.	[179]
	SRM® 1649b	25 μg/mL, systemic	2 and 24 h	- Increased IL-6, IL-1β, and IL-1α protein secretion, and mRNA expression. - Phosphorylation of p38 and AP-1.	[180]
	SRM® 1649b	50 μg/mL, systemic	UK	- Increased protein expression of COX2, PLA2, ICAM1, and MMP-9. - Phosphorylation of ERK, p38, and JNK.	[230]
	SRM® 1649b	50 μg/cm2, systemic	6 and 24 h	- Increased COX2 protein (24 h) and mRNA (6 h) expression. - Increased PGE2 protein secretion. - Phosphorylation of p38, ERK, JNK, and p65.	[181]
	SRM® 1649b	100–400 μg/mL, systemic	24 h	- Phosphorylation of ERK and JNK. - Increased MMP1 mRNA and protein expression.	[172]
	SRM® 1650b	Unknown	1 h	- Binding of PM to TLR5.	[169]
	SRM® 1650b	50 μg/mL, systemic	24 h	- Induced phosphorylation of ERK, p38, and JNK.	[182]
	SRM® 1650b	Unknown	3 h	- Increased IL-1β, IL-6, IL-8, IL-16, and TGF-β2 protein secretion. - Increased IL6 mRNA expression.	[169]
	SRM® 1650b	Unknown	24–72 h	- Increased IL-1β, IL-6, IL-8, IL-16, and TGF-β2 protein secretion. - Increased IL-6 protein expression (time-dependent increase). - Increased IL6 mRNA expression. - Increased TLR5 protein and mRNA expression. - Increased MyD88 protein expression. - Nuclear translocation of p65. - NOX4-TLR5 interaction.	[169]
	SRM® 1650b	50 μg/mL, systemic	24 h	- Phosphorylation of ERK, JNK, and p38.	[168]
	SRM® 1650b	50 μg/mL, systemic	30 m, 1 h, and 24 h	- Increased MMP-1 protein activity, expression, and mRNA expression. - Increased MMP-2 and MMP-9 protein expression. - Activation of the MAPK pathway. - AP-1 binding to MMP-1 promotor.	[185]
	SRM® 2975	100 and 200 μg/mL, systemic	30 m and 24 h	- Decreased IL-8 and CXCL10 protein secretion after 24 h. - Phosphorylation of p38, ERK, and JNK after 30 min.	[125]
	CAPs, PM2.5	5–25 μg/mL, systemic	1, 3, 6 and 24 h	- Nuclear translocation of p65. - Increased IL-1α protein secretion.	[145]
	CRM no. 28	125 μg/mL, systemic	30 m, 24 h post-incubation	- Nuclear translocation of p65. - Phosphorylation of p38, ERK, and JNK. - Increased PGE2, TNF-α, and IL-6 protein secretion. - Increased COX2 protein expression.	[137]
	CRM no. 28	125 μg/mL, systemic	30 m, 24 h post-incubation	- Nuclear translocation of p65. - Phosphorylation of p38. - Increased COX2 protein expression. - Increased PGE2, IL-6, TNF-α, and IL-1β protein secretion.	[231]
	ERM-CZ100 and ERM-CZ120	100 μg/mL, systemic	24 h	- Increased IL-1β, PGE2, and IL-6 protein secretion. - Increased COX2 protein expression.	[232]
	ERM-CZ120	100–400 μg/mL, systemic	24 and 48 h	- Increased PGE2 protein secretion.	[126]
HEK-001	SRM® 1650b	Unknown	24 h	- Increased IL-1β and IL-6 protein secretion. - Increased IL-6 protein expression.	[169]
JB6 P+, mouse cell line	SRM® 1975	10–20 μg/mL, systemic	12, 24, 36, and 48 h	- Activation of NF-κB. - No activation of AP-1. - Activation of the Akt/PI3K pathway. - Phosphorylation of ERK, not of p38 and JNK.	[233]

Abbreviations: h, hour; d, day; HSE, human skin equivalent; HEE, human epidermal equivalent; NHEK, normal human epidermal keratinocyte; SRM, standard reference material; PM, particulate matter; CAP, concentrated ambient particles; ppm, parts per million; CRM, certified reference material; CXCL10, C-X-C motif chemokine ligand 10; TLR, Toll-like receptor; IL, interleukin; MAPK, mitogen-activated protein kinase; TNF, tumor necrosis factor; MMP, matrix metalloprotease; NF-κB, nuclear factor kappa B; PGE₂, prostaglandin E2; AP-1, adaptor protein 1